rs1980493

Positions:

• chr6-32395438-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.1079-413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,118 control chromosomes in the GnomAD database, including 1,280 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1280 hom., cov: 32)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

Genes affected

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.1079-413A>G		intron_variant		ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-10016T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.1079-413A>G		intron_variant		5	NM_001304561.2	ENSP00000390613	P1
TSBP1-AS1	ENST00000645134.1	n.627+4685T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18806 AN: 152000 Hom.: 1281 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18813 AN: 152118 Hom.: 1280 Cov.: 32 AF XY: 0.117 AC XY: 8729 AN XY: 74366

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.0336

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.105

Alfa AF: 0.141 Hom.: 3002

Bravo AF: 0.118

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1980493; hg19: chr6-32363215;